RESEARCH OBJECTIVES: Histogenesis of the brain is regulated by finely specified cell recognition properties. These properties influence the patterns of cell proliferation, cell migration, and selective cell association that culminate in complex cytoarchitectural organization and synaptic networks. This research project is based on investigations of aggregating brain cell systems in vitro as analytical models for cell recognition during histogenesis. We plan to fabricate experimental aggregate tissues to analyze the developmental cell interactions that lead to the highly ordered cortical alignment of neurons in the mouse isocortex and to differences in patterns of cortical histogenesis between the avian and mammalian cerebrum. We will also design aggregates to examine the specificity of neuronal-glial interactions and the specificity of substantia nigra innervation of the caudate nucleus. In continuing our studies of cell-free, type-specific brain cell recognition factors, we will use the specific antisera we have obtained against the cerebrum recognition factor (CRF) to advance our purification procedures and to localize and characterize cell binding sites for CRF during histogenesis in situ and in vitro. Our major goal remains the complexing of purified CRF to collagen substrates in order to construct coded pre-neural pathways and elicit directed cell migration.